Liquid transport device, method of transporting a liquid, method of analyzing a liquid and test element for use in analysis of a liquid

Abstract

 A liquid spreading device and a method of spreading a liquid by means of this spreading device. The spreading device (10) includes opposed surfaces (16, 18) providing a capillary flow zone. Each surface (14,16) includes means (42, 44) for directing flow along predetermined paths and at least one surface (16) includes means (26)to permit liquid introduction between the surfaces (16, 18. At least a portion of the paths of one surface form a positive angle (a) with respect to the paths of the directly opposing portion of the other surface, whereby controlled multidirectional flow of liquid introduced between the surfaces occurs with a predetermined peripheral configuration. Also disclosed are methods of analyzing a liquid and test elements for them which includethe spreading device and the method of spreading the liquid.

Description

[0001] This invention relates to devices and methods for transporting liquid in controlled, predetermined flow patterns.

[0002] Various passive liquid transport devices, that is, those free of moving parts, have been designed to deliver liquid over defined surface areas. For example, liquids have long been spread between two generally smooth surfaces by the use of capillary action, to permit the study, usually microscopic, of the liquid's contents. Examples of such devices are disclosed in U.S. Patent Specifications Nos. 3,198,064 and 3,961,346.

[0003] The non-uniform smoothness of the-exposed surfaces in such devices, however, characteristically results in uncontrolled and undirected capillary flow of the liquid across those surfaces. The consequences of such uncontrolled flow include the possibility of forming trapped air pockets and thus the incomplete wetting of certain portions of the surface. Air pockets are particularly undesirable when undertaking automatic, possibly microscopic, examination of the liquid and/or the wetted surfaces. Such examination cannot tolerate the absence of the liquid in the relevant scanning area, as automated equipment is not capable of ignoring such unwetted areas. Air pockets are a common occurrence when wetting or filling zones of tortuous configuration, e.g., those containing corners around which the liquid must flow. Another consequence of uncontrolled flow is the formation of rapidly extending irregular streams. These streams when contacting other liquids induce considerable mixing of the liquids. Such mixing can be particularly undesirable when two dissimilar liquids are transported in a device to make a potentiometric measurement relating to the presence or concentration of a common ionic species.

[0004] It is an object of the present invention to overcome the aforementioned problems by providing a predetermined liquid flow pattern at a controlled rate across a desired surface area.

[0005] In accordance with the present invention there is provided a liquid transport device for inducing controlled flow of liquid, comprising two opposing surfaces spaced apart a distance effective to induce capillary flow of introduced liquid, and means to permit the introduction of liquid between said surfaces, characterized in that each of said surfaces includes, across at least a portion thereof, means for directing capillary flow of introduced liquid along predetermined paths,- said directing means on the respective surfaces being relatively oriented so that the paths directed by a substantial portion of one of said surfaces form positive angles with respect to the paths directed by the directly opposing portion of the other surface, whereby capillary flow of liquid between said surfaces occurs in a controlled multidirectional manner with a predetermined peripheral configuration.

[0006] In accordance with the present invention there is also provided a method of transporting a liquid, comprising the steps of introducing the liquid between two opposing surfaces which are spaced apart a distance effective to induce capillary flow in the liquid across a transport zone between said surfaces, characterized by directing a portion of the introduced liquid to flow across one of said surfaces along a predetermined first pattern of paths, and simultaneously directing another portion of the introduced liquid to flow across the other of said surfaces along a predetermined second pattern of paths, the paths of one surface forming positive angles with respect to the directly opposing paths of flow directed by the other surface.

[0007] In accordance with the present invention there is also provided a method of analyzing a liquid, wherein a property of the liquid is detected after it is spread across a defined area, comprising introducing the liquid between two opposing surfaces which sandwich the area and are spaced apart a distance effective to induce capillary flow in the liquid, characterized by directing introduced liquid across one of said surfaces along first predetermined paths, and directing introduced liquid across the other of said surfaces along second predetermined paths which form positive angles with respect to said first paths.

[0008] In accordance with the present invention there is also provided a method of analyzing a liquid, wherein a property of the liquid is detected after it is spread through a defined transport zone, characterized by transporting said liquid across the zone with a controlled peripheral configuration, comprising introducing the liquid between two surfaces having opposed surface areas in part bounding the transport zone and spaced a distance effective to induce capillary flow, each of said surface areas having a plurality of grooves constructed in a predetermined pattern, at least a portion of the grooves of one surface area forming a positive angle with respect to the directly opposed grooves of the other surface area.

[0009] In accordance with the present invention there is also provided a test element for use in the analysis of a liquid at a test site, including a liquid transport device for inducing liquid flow to said site, said device comprising two opposing surfaces spaced apart a distance effective to induce capillary flow of introduced liquid, and means to permit the introduction of liquid between said surfaces, characterized in that each of said surfaces includes, across at least a portion thereof, means for directing capillary flow of introduced liquid along predetermined paths, said directing means on the respective surfaces being relatively orientated so that the paths directed by a substantial portion of one of said surfaces form positive angles with respect to the paths directed by the directly opposing portion of the other surface, whereby capillary flow of liquid between said surfaces occurs in a controlled multidirectional manner with a predetermined peripheral configuration.

[0010] In accordance with the present invention there is also provided a test element for use in the analysis of a liquid comprising two opposing surfaces spaced apart a distance effective to induce capillary flow of introduced liquid, and means to permit the introduction of liquid between said surfaces, characterized by each of said surfaces including, across at least a portion thereof, means for directing capillary flow of introduced liquid along predetermined paths, said directing means on the respective surfaces being relatively orientated so that the paths directed by a substantial portion of one of said surfaces form positive angles with respect to the paths directed by the directly opposing portion of the other surface, whereby capillary flow of liquid between said surfaces occurs in a controlled multidirectional manner with a predetermined peripheral configuration, and by a reagent disposed on a portion of at least one of said surfaces for reaction with the liquid.

[0011] Embodiments of the present invention will now be described, by way of example, with reference to the accompanying drawings in which:

Fig. 1 is an isometric view of a transport device in accordance with the invention, the spacing between parts being exaggerated for clarity;

Fig. 2 is an enlarged, fragmentary sectional view of the device of Fig. 1, the width of the grooves and the spacing between surfaces being exaggerated for clarity;

Fig. 3 is a fragmentary perspective view taken generally along the line III-III of Fig. 2, portions of the liquid in contact with the upper member having been deleted for clarity;

Figs. 4-6 are plan views of devices similar to that shown in Fig. 1, illustrating several alternative embodiments thereof and, particularly, alternative liquid transport patterns;

Figs. 7a and 7b are fragmentary sectional views similar to Fig. 2, illustrating dimensional variables and alternative configurations of the device;

Figs. 8a and 8b are fragmentary sectional views illustrating the effect of varying angle beta;

Fig. 9 is an isometric view of an embodiment of the invention, in a device for analyzing ionic activity of electrolytes of a liquid;

Fig. 10 is a fragmentary sectional view taken generally along the line X-X in Fig. 9;

Fig. 11 is a plan view of the ion bridge included in the embodiment illustrated in Fig. _'9 illustrating the advancing liquid wave fronts during use; and

Fig. 12 is a fragmentary plan view of yet another embodiment of the invention.

[0012] Liquid transport devices in accordance with this invention are intended for transporting, also described as "spreading", any liquid over a surface area or through transport zones of many sizes and shapes, flat or curved, regardless of end uses, provided that the surfaces and liquid involved are capable of exhibiting capillarity and thereby provide capillary transport. The invention provides such transport in a controlled, multidirectional manner, to produce an area or zone of liquid having a predetermined peripheral configuration.

[0013] Although the embodiments hereinafter described are those in which the opposed members are generally flat, the invention is not so limited. Any two generally parallel surfaces with appropriate directing means can be used, provided the opposed surfaces are spaced apart a distance that will permit capillary flow of liquid introduced between the members. This distance need not be uniform throughout the device, that is, exact parallism need not be maintained, as long as capillary flow is maintained as further described hereafter. Useful "parallel" surfaces include curved parallel surfaces, e.g., cylindrical or spherical members one of which has a concave surface that is generally coaxial or concentric with an opposing convex surface of the other member.

[0014] In the ensuing description the liquid is introduced in the form of drops, but the liquid may be introduced in other forms.

[0015] Examples of liquids which may be transported by this device and methods in accordance with the invention include both aqueous and non-aqueous liquids with or without dissolved, dispersed, or emulsified addenda. Devices and methods in accordance with the invention have been found particularly useful for transport of blood and blood serum.

[0016] In Figs. 1-3 there is illustrated a liquid spreading device 10, in accordance with the invention, which comprises two members 12 and l4 having opposing surfaces 16 and 18, respectively, additional edge surfaces 20,22, and back surfaces 24 on the sides of the members 12 and 14 opposite to surfaces 16 and 18. Means are provided on surfaces 16 and 18 to control and direct flow of liquid across at least a portion of, and preferably the entire area of, those surfaces. The surfaces 16 and 18 of the members 12 and 14 are spaced apart by a distance "s" (See Fig. 2). Distance "s" is selected to ensure that capillary flow of liquid will occur between surfaces 16 and 18, under the influence of directing means. As used herein, "capillary flow" or "capillary transport" is that flow or transport of liquid that occurs between confining surfaces, wettable by that liquid, due to surface tension in the meniscus of the liquid between the surfaces. As is well known, capillary flow is a function of the distance "s" between the confining surfaces, and the limit to which such distance "s" can be extended depends upon the properties of a given liquid. The distance "s" and the area of surfaces 16 and 18 define approximately the volume of the transport zone.

[0017] The two members 12 and 14 can be held apart distance "s" by a number of constructions, such as a spacer member (not shown) interposed at appropriate intervals through portions of the transport zone. Alternatively, surface 16 can be supported spaced away from surface 18 by means located along or adjacent to edge surfaces 20 and 22.

[0018] As will be evident, at least one of surfaces 16 and 18 is selected from a wettable material that is substantially impervious to the liquid to be transported. A "wettable surface" is one which, for the liquid to be transported, provides a liquid-vapour contact angle which is less than 90°. Such a contact angle ensures the liquid will wet the surfaces to some extent, and is in contrast to the angle that exists when using the same surface material with a liquid such as mercury. As used herein, a "substantially impervious" surface or material is one with respect to which substantially all of the liquid to be transported will move across, rather than penetrate through or into to any appreciable extent. A highly useful embodiment is one wherein both surfaces 16 and 18 comprise a material that is substantially impervious to the transported liquid. As will also be apparent, any listing of such materials depends upon the nature of the particular liquid to be tra^psported, and selection of the appropriate material will be readily evident in the light of knowledge of the properties of such liquid.

[0019] To permit liquid to be introduced into the transport zone, a liquid access aperture 26 is provided in member 12. The aperture 26 extends from surface-24 to surface 16 and is in a region of member 12 overlying the surface 18. The size and shape of the aperture 26 preferably are such as will direct liquid into contact with the surfaces bounding the transport zone. That is, both the surfaces 16 and 18 must be wetted by the continuous volume of the drop, and aperture 26 has a configuration that is not too small to permit this. The transverse dimension of the aperture 26 can also be so large as to prevent contact between the surface 24 and a centred drop. A suitably sized drop should have a volume which at least equals the sum of the volume of aperture 26 and the volume of the transport zone that is to be filled by the liquid. In one embodiment of the invention convenient drop volumes are those between about 5 and about 1000 µl. The choice, of course, depends upon the end use of the device. For best results in driving the drop of liquid into the centre of the aperture 26, and thus into the transport zone, it is preferred that the shape of the aperture 26 be a regular hexagon (not shown) rather than a circle.

[0020] Alternatively, the space between members 12 and 14 left exposed at either edge surface 20 or 22 can serve as the means to permit the liquid to be introduced. As with aperture 26, the spacing between surfaces 16 and 18 preferably causes the liquid to wet both surfaces.

[0021] A highly preferred form of the directing means comprises a pattern of exposed grooves 42 and 44 related to the surfaces 16 and 18 respectively. Herein the term "groove" refers to a channel, depression or the like and thus each of grooves 42 and 44 is (Fig. 2) the space between two adjacent ridges 46 and 48, respectively. The grooves and ridges of one surface are disposed at an angle alpha (a) with respect to the grooves and ridges of the other surface, as is described in detail hereinafter. Each ridge has a top portion 50 which in the embodiment of Figs. 1 to 3, is an edge.

[0022] Figs. 2 and 3 illustrate the manner in which device 10 is effective to provide controlled multidirectional flow. A quantity of liquid "L" of a volume sufficient to wet both surfaces 16 and 18 is placed in aperture 26. However, the condition shown in Fig. 2 is unstable and immediately the menisci m₁ and m₂ of the liquid move to the positions shown in broken lines, filling the width of one groove 42. Meanwhile flow also advances along the length of groove 42. Thus a multidirectional flow soon develops, providing a peripheral configuration comprising wave fronts that conform to the linearity, or curvilinearity of the grooves or ridges.

[0023] An understanding of the physical explanation for the linearity or curvilinearity of the wave fronts is believed not necessary to the practice of the invention, and it is not completely understood. However, it is presently believed that, because of edge effects, the grooves act as repeating energy barriers to the capillary flow of liquid moving transverse to those grooves. Transverse flow in the case of the groove 42 is in the direction of the arrows 52 in Fig. 2. As is well known, the surface discontinuities created at the top edges 50 of the ridges create energy barriers to capillary flow. Each of the barriers is completely confronted and overcome before the next one is confronted and breached. Thus, in Fig. 2, if only a portion of the meniscus m₂ reaches the left-hand ridge 46', the groove 42' beyond that ridge is a barrier to further flow of meniscus m₂ leftwards in Fig. 2 until the rest of the liquid flowing across groove 42 reaches that ridge 46'. More precisely, although the energy levels favour movement of the liquid to the top edge 50 of ridge 46', the edge at 50, created by the adjacent groove 42', is a temporary energy barrier to flow by the meniscus m₂ into groove 42'. Less energy is required to pull any remaining, lagging portion of meniscus m₂ up to the top edge 50 of ridge 46' than is required to move the leading portion of the meniscus m₂ shown in broken lines at ridge 46', beyond that ridge. When the ridge 46' is reached for the full length of the groove 42 that is carrying liquid, there remains no effect favouring the filling of groove 42 only up to ridge 46'. At that time, i.e. when the ridge 46' is reached for the full length of the groove 42 carrying liquid, assuming sufficien liquid remains in aperture 26, there is in the liquid sufficient energy to overcome the energy barrier represented by the groove 42' beyond ridge 46'.

[0024] Thus, a portion of meniscus m₂ moves to the next left-hand ridge (not shown). When that occurs, the energy levels favour the movement of all of meniscus m₂ to that next ridge before movement continues beyond that next ridge. Looking at the behaviour from another viewpoint, liquid flow along groove 44 in member 14 appears to be controlled by the energy barriers presented by the grooves and ridges, to jump repeatedly from ridge 46 to ridge 46, one ridge at a time. As a result, a wave front 60 is formed (see Fig. 3) having the linearity or curvilinearity of ridges 46. The wave front 60 advances in the direction of arrows 62.

[0025] In the meantime, the same behaviour is occurring with respect to flow along the length of grooves 42 in the direction of arrows 66 (see Fig. 3)_. That is, ridges 48 of the surface 18 of member 14 create similar energy barriers and flow along the length of grooves 42 will "hesitate" at a ridge 48 rather than cross the energy barrier presented by the groove 44 beyond. Only wnen a wave front has completely reached a given ridge 48 is there no favour to movement only up to that ridge. Thus, wave fronts 64 are formed such that, when a portion of the wave front 64 moves to the next adjacent ridge 48, the energy levels favour the movement of the trailing portions of the wave front 64 to that ridge 48 before the leading portion of the wave front 64 can move on. As a result, wave fronts 64 take on the linearity or curvilinearity of ridges 48.

[0026] The ridge-jumping process continues until there is no more liquid L in aperture 26 to feed the advancing wave fronts 60 and 64, or until the capillary spacing between surfaces 16 and 18 terminates at a boundary of the transport zone, such as at edge surfaces 20 or 22, which prevent further capillary flow. If capillary flow ceases because of an open boundary such as at edge surfaces 20 or 22, such a boundary can be described as a flow-terminating energy barrier.

[0027] Because of the flow control provided by the grooves and ridges, portions of the wave fronts 60 and 64 do not accidentally meet each .other and confine and trap an air pocket in the transport zone. Instead, the entire area of surfaces 16 and 18 is wetted, and the entire transport zone, defined by such surface areas and the space between them, is filled. Of course, should it be desired, controlled flow to form an air pocket could be achieved.

[0028] The preceding discussion of the liquid wave fronts is based upon the flow as viewed overall, in plan. As shown in Fig. 4, when a drop of liquid L is introduced at aperture 26, it encounters surfaces provided with substantially parallel rectilinear grooves. The wave fronts 60 and 64 that form are substantially rectilinear and remain so as the flow proceeds to and beyond the positions 60f and 64', respectively, indicated in broken lines.

[0029] Thus, the multidirectional flow achieved by the device as described is the overall flow occurring in two or more non-aligned directions. The multidirectional flow can occur generally in a-planar manner, if the opposed surfaces are generally flat, or it can occur three dimensionally if the surfaces are curved.

[0030] It will be understood, however, that the microscopic details of the wave fronts are probably more complex. The view in Fig. 3 is only an estimate of the microscopic shape of such wave fronts, especially as seen in elevation. It is believed the wave fronts actually have a curvature about an axis, and specifically that wave front 60 has an axis of curvature 68 and wave front 64 an axis of curvature 70. However, whatever the actual microscopic curvature of the wave fronts, e.g., as might appear in a perspective view such as Fig. 3, it is distinct from the observed overall linearity or curvilinearity of the wave fronts when viewed in plan.

[0031] The pattern of grooves of each surface is preferably continuous; that is, each groove extends either all the way across surface 16 or 18, from an edge surface 20 or 22 to the opposite edge; or the groove closes upon itself, as in a closed curve, without a break. However, small breaks in the ridges forming the grooves can be tolerated as they will affect the control of the wave fronts to only a negligible extent.

[0032] As will be seen, each of the grooves has a substantially greater length than width. Each pattern of grooves, e.g., grooves 42, provides at least a first predetermined series of flow paths, that is, in the directions of the grooves' lengths. Such directions are the primary flow directions of the grooves. In Figs. 1 and 2, grooves 42 are illustrated as having their lengths extending in substantially parallel straight lines, providing essentially straight flow paths. The pattern of grooves 44 provides at least a second predetermined series of flow paths, extending in the directions along the lengths of grooves 44. Grooves 44 (Figs. 1 and 2) are also illustrated as having a length extending in substantially parallel straight lines. The grooves of the respective surfaces are disposed so that the grooves, and therefore the paths of flow, of one surface form an angle a with respect to the directly opposed portions of the grooves and therefore the paths of flow, of the other surface (see Figs. 1 and 3). The term "directly opposed" as used in reference to a portion of a path or groove of a surface, means a portion that is disposed directly above or below a point, hereinafter "superposition point", on a respective path or groove of the other surface. The angle existing between the two paths or the two grooves of the two surfaces, at the superposition point, is angle a.- Preferably angle a is measured in a plane parallel to one of the surfaces at the superposition point.

[0033] Angle a is positive, that is, non-zero, for at leatt a portion of the transport zone, and in the case of the patterns of Fig. 1, for the entire transport zone. It is the presence of this positive angle that ensures that liquid L introduced at aperture 26 will flow through the transport zone in the controlled, multidirectional manner described above. The actual shape or pattern of such overall flow depends upon the value or values of a, the flow rate within the grooves, as described hereinafter, and the curvilinearity, if any, of the ridges (or grooves). As shown in Fig. 1, a can be 90°, and in these instances, with substantially parallel, straight grooves 42 and 44, a substantially rectilinear flow pattern proceeds (see Fig. 4). That is, wave fronts 60 and 64 are generally perpendicular to each other to provide a predetermined peripheral configuration controlled to the shape of a rectangle. After a passage of time, the wave fronts 60' and 64' are still generally perpendicular.

[0034] In Fig. 5, angle a has a value of 45°. As the grooves in both the members are again substantially straight and parallel, the boundary of the spread liquid at any time in spreading while the spreading is solely under the control of the grooves and ridges,is rhomboidal, as delineated by wave fronts 74 and 76.

[0035] In the embodiment represented in Fig. 6, curvilinear grooves are utilized in one member. Parts similar to those previously described bear the same reference, to which the distinguishing suffix "a" has been added. In device 10a grooves 42a, visible through transparent member 12a, are concentric circles centred upon aperture 26a. Grooves 44a are substantially straight and parallel as before. A region in which spread has occurred and which is bounded by the advancing wave fronts 80 has the form shown. The long axis extends in the direction of straight grooves 44a. In such a case, angle a varies within the pattern from 0° to 90°. Flow of wave front 80 proceeds least rapidly along a line which passes through the geometric centre of the concentric grooves and which is perpendicular to the direction of the linear grooves. It is along this line that angle a becomes zero for the infinitesimal portions of the linear grooves that are tangent to the directly opposed circular grooves.

[0036] Other curvilinear patterns are also possible, e.g., sine wave patterns (not shown).

[0037] It will be appreciated that it is usually of little consequence which of the two members, upper or lower, has which pattern of grooves, so long as at least the portion of the directly opposed grooves over which control of flow is desired form a positive angle a as described above.

[0038] Certain dimensional variables can provide variations in the performance of device 10. Conveniently, the width "w" of the grooves (see Figs. 2 and 7a) is defined as the distance from top portion to top portion of adjacent ridges, and the thickness "t" of the ridges is the thickness of the ridges at their base, (see Figs. 2 and 7a). As noted, distance "s" is the distance between surfaces 16 and 18, i.e., between the bottom surfaces of the opposed grooves. Each ridge of the type shown, whether truncated or peaked, forms an included angle P (see Fig. 7a). The depth of grooves 42 is "d_l" and of grooves 44 is "d₂", and the amount of truncation of the ridges 46, if any, is "d₃" (or "d₄" for ridges 48). Each groove or ridge has a radius of curvature "R", R being infinite if the ridges are rectilinear.

[0039] The dimensions chosen for s, w, t, β,R, d_l3 d₂, and d₃ can vary, depending upon the liquid being transported, the extent to which it wets surfaces 16 and 18, and the intended use of the liquid so transported. In all cases, capillary flow should be maintained across the surfaces 16 and 18 within the transport zone at a rate that is consistent with the intended end use. The selection of particularly desired values of the noted variables to provide a particular capillary flow is a matter of design-choice. For uses that require certain lesser flow rates, distance can be no greater than d_l plus d₂₁ that is, top portions 50 of ridges 46 can contact top portions 50 of ridges 48 (Fig. 7b). However, in such instances w should be selected so that multidirectional flow will be achieved notwithstanding a value for s equal to only d₁ plus d₂. If w is reduced below such larger values, when s=(d₁ + d₂), the transport time (or time of spreading) can become prolonged beyond useful values.

[0040] The value of w need not be uniform across an entire pattern, but can be variable, as shown, for example, in Fig. 7a. For example, w_n can be chosen to be equal to n times the width of w₁. Alternatively, each w can be of random width. However, the width w of grooves 42, for example, does partially control, along with depth d₁ or d₂₁ the rate of advance of the wave front within those grooves. The rate has been found to vary roughly as an inverse function of the cross-sectional area of the groove (i.e. the cross-sectional area transverse to the direction of flow along the length of the groove). That is, the smaller the transverse cross-sectional area of a groove, the faster is the rate of advance of the wave front along that groove because of capillary action. Furthermore, where the grooves 42 and 44 have uniform cross-sectional areas different one from the other, the direction of the grooves having the smaller value of that area will be the dominant flow direction.

[0041] Included angle p in either of the-ridges (e.g., 46, Fig. 8a) forming the grooves can become critical if it is too large, or if it is so small as to prevent proper capillary attraction of the liquid being transported, whether or not the ridges are truncated. For most liquids and most materials used in the manufacture of either member 12 or 14, a preferred value for angle P is about 90°. Values of angle β much greater than this tend to cause a loss in control of the advance of the wave front, because the surface formed by the bottoms of the grooves and the surfaces of the ridges approaches a smooth surface. As stated above, a smooth surface lacks control. Smaller values of angle p can be used, even as small as about 10° (see Fig. 8b). When using small values of angle β and non-truncated ridges, unless the dimension w, i.e. the spacing between the ridges, is increased, the liquid might not completely wet the grooves. Although such a design is still useful, the best control over the peripheral configuration of the transported liquid occurs when the grooves are completely wetted. To ensure complete wetting, an increase in dimension w, i.e., spacing between ridges, can be obtained by the effective elimination of one or more next adjacent ridges (shown in broken lines in Fig. 8t), producing flat-bottomed grooves 42. The value of w required is a function of the liquid being transported, specifically its surface tension, as well as of its ability to wet the material forming the surface.

[0042] Larger values of angle β, e.g.,, up to about 90°, can also be used in the embodiment shown in Fig. 8b. However, care must be taken that w is not so large that capillary flow is lost or the flow rate becomes too slow.

[0043] The preceding analysis assumes that the demarcation between the surface 16 or 18, i.e. the bottoms of the grooves, and the side surfaces of the ridges 46 or 48 is a sharp line of intersection, and that top portions 50 of the ridges form a sharp edge of intersection with the side surfaces of the ridges. However, curved surfaces can be used for the surface 16 or 18 or top portions 50, so that there is no clear line of intersection. In such instances, dimensions t, w and angle β can be approximated only.

[0044] The above-described grooves can be formed by a number of conventional techniques, including solvent-softening techniques and embossing techniques. For example, a grooved roller opposed by a pressure roller can be used in the presence of a solvent mist to create a permanent set in the material as it passes through the rollers.

[0045] As noted, it is believed that the wave front configuration is determined by energy barriers. It is such energy barriers that confine the flow across each surface 16 and 18 to certain predetermined paths. Other means, which are not illustrated, can be used for directing capillary flow along predetermined paths. Such other means may include permanent surface treatments of strip portions of generally hydrophobic surfaces 16 and 18 to provide substantially parallel strips that are more hydrophilic than the strips between them. Useful known processes to increase the hydrophilicity of hydrophobic plastic surfaces include a) exposing those strip portions of the surface which are to become more hydrophilic, to corona discharge, for example, as disclosed in U.S. Patent Specification No. 3,376,208; b) flaming those strip portions (to be more hydrophilic) with a flame at a temperature between about 885°C and about 2000⁰C for a fraction of a second, for example, as disclosed in U.S. Patent Specification No. 3,072,483; c) wetting the strip portions (which are to be more hydrophilic) with a weak acid solution of H202 prior to exposing the wetted portions to UV radiation, e.g., as disclosed in U.S..Patent Specification No. 3,360,448.

[0046] The purpose of spreading or transporting the liquid through the entire transport zone of device 10 is not critical to the invention. Examples of such purposes include, for example, clinical analysis of analytes of the liquid, and rapid dissolution of certain reagents distributed in the transport zone for reaction with components of the liquid. In those instances in which members 12 and 14 are formed of a transparent material, the liquid and its components can be examined under a microscope. In some of such uses, it can be desirable to include a reagent disposed on at least a portion of one or both of the surfaces, such as a buffer, a lysing agent in the case of blood analysis, and/or a compound capable of reacting with the liquid to generate a detectable change. An example of the last-mentioned example is described in U.S. Patent Specification No. 3,992,158.

[0047] Yet another use of the device is as a means for providing controlled distribution of the liquid at a uniform rate along the entire edge surface 20 or 22 (see Fig. 1). If liquid is removed along such edge surface, the transport device 10 ensures that the rate of flow of liquid to that edge surface is controlled and uniform along that entire edge surface.

[0048] An embodiment of the invention is particularly useful in the potentiometric analysis of blood serum. In such an embodiment the serum is spread to a test site where it contacts an adjacent electrode. In the ensuing description parts similar to those previously described bear the same reference numeral but with the distinguishing suffix "b" added. In Figs. 9 to 11 there is illustrated a device lOb comprising an ion bridge in an apparatus 100 that also includes a frame 102 which mounts a pair of ion- selective electrodes (hereinafter, "ISE") 104. The ISE's 104 are bridged by device 10b. As described in detail in U.S. Patent Specification No. 4,053,381, the details of which are expressly incorporated herein by reference, each ISE 104 is a generally flat multilayered element comprising adjacent layers 106-110 (see Fig. 10). When a drop of liquid A or B (Fig. 10) makes contact with layer 106, which is an ion- selective membrane, the ion Z

of choice which is an analyte of the blood serum, is carried, or otherwise penetrates, to the underlying layers 107-108 where an electrical potential is generated based upon the activity of that particular ion. Layer 107, for example, can be a dried hydrophilic binder containing the salt Z^⊕X^⊖. Layer 108 in such instances is the X^⊖ salt of an electrically conductive metal M^⊕. Metal M° forms layer 109. Because layer 109 is an electrically conductive layer, the potential can be detected by electrometer 116 via probes 114 which penetrate into contact with layer 109 at windows 112. Any difference in the two potentials due to two different ion activities of the two liquids A and B, (one an unknown and one a reference having a known concentration of Z^⊕, is registered as a difference potential on the electrometer 116. This reading then can be converted into a measure of concentration of the ionic analyte Z^⊕.

[0049] A pair of apertures 26b and 118, and 26b' and 120, are formed one above each ISE 104 as liquid access apertures (Fig. 10). It is through these aperture pairs that the two drops of liquid A and B move to contact the ISE's, as shown by arrows 122. The apertures 26b, 26b' are in the member 12b and the apertures 118, 120 are in the member 14b.

[0050] Device 10b is used to provide means for ionically connecting the liquid of drop A to the liquid of drop B, whereby an electrical circuit including the ISE's and the electrometer is complete. This connection of the liquids A and B is achieved by the use of members 12b and 14b having opposing surfaces each of which bears a pattern of grooves 42b and 44b, which can be for example sawtooth in shape. Grooves 44b extend from at least the vicinity of aperture 26b to at least the vicinity of aperture 26b', and are preferably substantially parallel and straight. Grooves 42b are superimposed over grooves 44b at an angle a of preferably about 90°, and are also substantially parallel and straight. As shown, grooves 42b and their bounding ridges 46b have a width w and thickness t, which may respectively be about 13 microns. The same or different dimensions can be used for grooves 44b and their bounding ridges. Grooves 42b, as illustrated in Fig. 10, represent a groove pattern as it would appear magnified approximately 700 times.

[0051] Member 12b is spaced from member 14b by edge walls 124, so that grooves 42b are spaced from grooves 44b a distance effective to provide capillary flow of liquid from drops A and B within the space. Walls 124 can be affixed to member l4b by means such as adhesive. Preferably, at least a portion of the space between grooves 42b and 44b is left exposed at edge surfaces 20b of device 10 (see Fig. 9) whereby air can be vented as the menisci advance.

[0052] Alternatively, the two members 12b, 14b can be welded together at appropriate positions, such as by ultrasonic welding, to form bridging studs (not shown) that space the members 12b, 14b apart. For example, such welding of the two members 12b, 14b at two pairs of relatively small spots, each located so as to bracket apertures 26b and 26b', provides the desired spacing.

[0053] Thus, the drops not only penetrate apertures 118 and 120 to contact ISE's 104, they also follow arrows 130 to form two advancing wave fronts 132, (see Fig. 11). Because grooves 42b and ridges 46b are rectilinear, so are wave fronts 132. Because ridges 46b are parallel throughout device lOb, the wave fronts when they meet form a junction 134 of minimum width between the two different liquids A and B. The junction 134 is shown in broken lines in Fig. 11. Such minimum width of junction 134 results in a minimum of intermixing, which in turn ensures that only liquid A will contact its electrode 104 and only liquid B will contact its electrode 104. Furthermore, a minimum width of intermixed liquid at junction 134 is desirable as it provides a stable junction potential and therefore a stable bias rather than a continuously varying bias.

[0054] To ensure a junction of such minimum width, it is preferred that the flow from apertures 26b and 26b' along grooves 42b fills the width of the bridge from edge 20b to the opposite edge 20b before flow along grooves 44b results in the meeting of the wave fronts 132 at junction 134. One way in which this can be achieved is by making the cross-sectional area transverse to flow along groove 42b smaller than the corresponding area of groove 44b. Alternatively, if junction 134 generally occurs one-half the distance between apertures 26b and 26b', and the distance of junction 134 from each aperture 26b and 26b' equals, or preferably exceeds, the spacing.of the apertures from the edges 20b of the zone, then such cross-sectional areas for grooves 42b and 44b can be equal.

[0055] For use as described, the grooved surfaces of both members 12b and 14b preferably comprise materials that are substantially impervious to blood serum. Examples of such materials include acetates such as cellulose triacetate, cellulose acetate propionate, and cellulose acetate butyrate; polystyrene; polyethylene; polypropylene; ABS plastic; and polycarbonate.

[0056] In the transport of blood serum, such as in the above-described use, the following groove pattern variables have been found to work satisfactorily. For cellulose triacetate material having grooves with a depth d₁ of between about 3 and about 15 microns, w=t, and a w/d_l ratio (see Fig. 8a) between about 0.35 and about 7.5, the spacing s between the two surfaces can be varied between about 0.06 mm and about 0.6 mm for best results. Lesser values of s can be used, except that when the separation distance s approaches d₁ plus d₂, spreading through the zone becomes extremely slow. Values of s greater than about 0.6 mm can in some cases destroy the capillary effect and thus the control over the wave front shape and rate of movement.

[0057] A preferred range for the width w of the grooves is between about 5 microns and about 5 mm, it being noted that beyond about 5 mm, the rate and direction of spreading becomes so ill-defined as to be insignificantly improved over the control achievable by two smooth surfaces.

[0058] Two representative examples for the above-described potentiometric analysis of blood serum are as follows:

Example 1

[0059] 

w (for member 12b) = 13.3 microns

w (for member 14b) = 13.3 microns

t (for member.12b) = 13.3 microns

t (for member 14b) 13.3 microns

s = 63.6 microns

beta = 90°

^d₁ ⁼ 6.8 microns

^d₂ ⁼ 6.8 microns

Example 2

[0060] For each of the surfaces:

w = 87.0 microns

t = 1750 microns

s = 250 microns

beta = 60°

d₁ and d₂ each = 75 microns

[0061] In such an example the ridges are truncated to such an extent that the operative surface of each member might be regarded as a smooth surface having widely spaced grooves.

[0062] For either example, to ensure that the liquid A, B of each drop does not contact the wrong electrode 104, a useful spacing of holes 26b and 26b' is about 1 cm when the diameter of the holes is about 3 mm. A useful width of the entire bridge transport zone in such instances, from edges 20b to 20b, is about 6 mm.

[0063] The embodiment illustrated in Fig. 12 demonstrates the ability of a passive device constructed pursuant to the invention to transport liquid around corners within the transport zone. Parts similar to those previously described bear the same reference numeral to which the distinguishing suffix "c" has been added.

[0064] Thus, device 10c includes a lower member 14c and an upper member 12c superimposed over the lower member. The respective opposing surfaces of the two members 12c, 14c are both grooved as in the previous embodiment, for example with substantially linear, parallel grooves. The angle a between superimposed grooves can be any positive value, e.g., 90° as shown. Aperture 26c permits introduction of liquid, as in previous embodiments.

[0065] Unlike the previous embodiments, the boundaries of the transport zone (which can be exposed edges of the transport zone adjacent edge surfaces 20c or 22c or portions of additional closure walls such as edge wall 124 illustrated in Fig. 10) are disposed to provide isolated tests areas 136 and 138, and corners 140, 142 and 144 within the transport zone which must be negotiated in a predictable manner by the transported liquid. Each of these corners 140, 142, 144 represents the point at which a portion of the zone boundaries form an interior angle that is greater than 180°, e.g., in the illustrated example, an interior angle of 270°.

[0066] Thus, the transport zone is divided by corner 140 into two leg portions 150 and 152, portion 150 containing aperture 26c. Portion 152 in turn has extending from it, at corners 142 and 144, respectively, test portions 136 and 138. In order for liquid to pass from aperture 26c into leg portion 152, it must turn corner 140. For the liquid in portion 152 to move into test area 136, it must turn corner 142. To move into test area 138 from portion 152, it must turn corner 144. Such a transport device can be defined as one in which the transport zone boundaries are so disposed that they permit an imaginary straight line, broken line 164, Fig. 12, to be drawn between two points X and Y on one or more of the boundaries, such as boundary 160 and boundary 162, respectively, without traversing the transport zone. It is of course the presence of corner 140 which permits such a line 164 to be drawn.

[0067] Alternatively, corners 140, 142 and 144 can be curves with no points of discontinuity (not shown), and it is around such curves that the liquid is transported. Such curves provide equivalent interior angles of greater than 180°.

[0068] It will be apparent that such a construction permits a plurality of separate tests to be conducted, e.g., in areas 136 and 138, using only a single drop of sample liquid. That drop flows in the direction of arrow 168, first to fill leg portion 150, then to fill leg portion 152 up to corner 142, at which time area 136 fills while the rest of leg portion 152 fills up to corner 144. Test area 138 is then the last area to fill. Each of the transport .zone boundaries blocks flow from occurring outside the zone. The test areas are isolated in the sense that liquid flowing to test area 138 has not flowed through test area 136.

[0069] At the same time as leg portion 150 is being filled, the drop flows in the opposite direction, arrow 170, to other portions of the zone (not shown), which can be, e.g., a mirror image of portions 150, 152, 136 and 138.

[0070] Any desired use can be made of isolated areas 136 and 138. That is, two different analyses of the liquid components can be made at those two portions of the zone.

[0071] Without the directing means such as the grooves of members 12c and 14c, and the positive value of angle a, it would not be possible to predict that an adequate flow of liquid would reach test areas 136 and 138, and if it did, at what time. Furthermore, flow into the test areas would at best be non-uniform.

Claims

1. A liquid transport device for inducing controlled flow of liquid, comprising

two opposing surfaces spaced apart a distance effective to induce capillary flow of introduced liquid, and means to permit the introduction of liquid between said surfaces, characterized in that

each of said surfaces includes, across at least a portion thereof, means for directing capillary flow of introduced liquid along predetermined paths, said directing means on the respective surfaces being relatively oriented so that the paths directed by a substantial portion of one of said surfaces form positive angles with respect to the paths directed by the directly opposing portion of the other surface, whereby capillary flow of liquid between said surfaces occurs in a controlled multidirectional manner with a predetermined peripheral configuration.

2. A device according to claim 1, characterized in that directing means of each of said surfaces comprises a pattern of grooves.

3. A device according to claim 2, characterized in that said grooves of at least one of said surfaces are substantially straight and parallel across said surface portion, whereby a substantially linear wave front is formed between said surfaces as the introduced liquid advances across said straight grooves.

4. A device according to claim 2, characterized in that said grooves of both of said surfaces are substantially straight and parallel, and wherein said angles are about 90°, whereby liquid introduced between said surfaces advances as at least two generally linear wave fronts mutually perpendicular to one another.

5. A device according to claim 2, characterized in that said grooves of one of said surfaces are curvilinear and substantially parallel, whereby liquid introduced between said surfaces advances as a curvilinear wave front.

6. A device according to claim 2, characterized in that said grooves are separated by ridges and the top portions of the ridges of one of said surfaces are spaced from the top portions of the ridges of the other surface.

7. A device according to claim 2, characterized in that said grooves are separated by ridges and the top portions of the ridges of one of said surfaces are in contact with the top portions of the ridges of the other surface.

8. A device according to claim 2, characterized in that the grooves of one of the surfaces have smaller cross-sectional areas than the grooves of the other surface to provide preferential flow in the direction of the grooves of said one surface.

9. A device according to any one of the preceding claims, characterized in that at least one of said surfaces is formed of a material that is substantially impervious-to the introduced liquid.

10. A device according to any one of the preceding claims, characterized in that the means to permit the introduction of liquid between said surfaces comprises an aperture in one of said surfaces.

11. A liquid transport device according to claim 1, characterized in that the means-for directing capillary flow includes strip portions of the surfaces which are alternately relatively hydrophille and relatively hydrophobic.

1₂. A liquid transport device according to claim 11, characterized in that the relatively hydrophilic strips have been formed by treating the relatively hydrophobic surface to corona discharge in the strip regions whose hydrophilicity is to be increased.

13. A liquid transport device according to claim 11, characterized in that the relatively hydrophilic strips have been formed by treating the relatively hydrophobic surface to flame at a temperature between 885°C and 2000°C in the strip regions whose hydrophilicity is to be increased.

14. A liquid transport device according to claim 11, characterized in that the relatively hydrophilic strips have been formed by wetting the strip regions whose hydrophilicity is to be increased with a weak acid solution of H₂0₂ prior to exposing the wetted portions to Ultra Violet radiation.

'15. A method of transporting a liquid comprising the steps of

introducing the liquid between two opposing surfaces which are spaced apart a distance effective to induce capillary flow in the liquid across a transport zone between said surfaces, characterized by

directing a portion of the introduced liquid to flow across one of said surfaces along a predetermined first pattern of paths,

and simultaneously directing another portion of the introduced liquid to flow across the other of said surfaces along a predetermined second pattern of paths, the paths of one surface forming positive angles with respect to the directly opposing paths of flow directed by the other surface.

16. A method according to claim 15, characterized by directing the flow across at least one of said surfaces to advance as a linear wave front.

17. A method according to claim 15, characterized by directing the flow across at least one of said surfaces to advance as a curvilinear wave front.

18. A method of analyzing a liquid, wherein a property of the liquid is detected after it is spread across a defined area, comprising:

introducing the liquid between two opposing surfaces which sandwich the area and are spaced apart a distance effective to induce capillary flow in the liquid, characterized by

directing introduced liquid across one of said surfaces along first predetermined paths, and

directing introduced liquid across the other of said surfaces along second predetermined paths which form positive angles with respect to said first paths.

19. A method of analyzing a liquid, wherein a property of the liquid is detected after it is spread through a defined transport zone, characterized by
transporting said liquid across the zone with a controlled peripheral configuration, comprising introducing the liquid between two surfaces having opposed surface areas in part bounding the transport zone and spaced a distance effective to induce capillary flow, each of said surface areas having a plurality of grooves constructed in a predetermined pattern, at least a portion of the grooves of one surface area forming a positive angle with respect to the directly opposed grooves of the other surface area.

20. A test element for use in the analysis of a liquid at a test site, including a liquid transport device for inducing liquid flow to said site, said device comprising

two opposing surfaces spaced apart a distance effective to induce capillary flow of introduced liquid, and means to permit the introduction of liquid between said surfaces, characterized in that

each of said surfaces includes, across at least a portion thereof, means for directing capillary flow of introduced liquid along predetermined paths, said directing means on the respective surfaces being relatively orientated so that the paths directed by a substantial portion of one of said surfaces form positive angles with respect to the paths directed by the directly opposing portion of the other surface,

whereby capillary flow of liquid between said surfaces occurs in a controlled multidirectional manner with a predetermined peripheral configuration.

21. A test element for use in the analysis of a liquid comprising

two opposing surfaces spaced apart a distance effective to induce capillary flow of introduced liquid, and means to permit the introduction of liquid between said surfaces, characterized by

each of said surfaces including, across at least a portion thereof, means for directing capillary flow of introduced liquid along predetermined paths, said directing means on the respective surfaces being relatively orientated so that the paths directed by a substantial portion of one of said surfaces form positive angles with respect to the paths directed by the directly opposing portion of-the other surface, whereby capillary flow of liquid between said surfaces occurs in a controlled multidirectional manner with a predetermined peripheral configuration, and by

a reagent disposed on a portion of at least one of said surfaces for reaction with the liquid.

Drawing